ZIOPHARM Oncology, Inc., a biopharmaceutical company focused on the development of new cancer therapies, has announced the expansion of synthetic immuno-oncology programs in conjunction with Intrexon Corporation, to include chimeric antigen receptor T-cell (CAR-T) therapy.
Additionally, ZIOPHARM has updated its development efforts regarding their proprietary RheoSwitch Therapeutic System® (RTS®) platform, an inducible regulator for expression of therapeutic molecules through administration of an oral activator ligand, alongside its clinical program with Ad-RTS-IL-12, a novel DNA-based therapeutic candidate for the controlled expression of IL-12.
CAR-T cells are engineered receptors that insert an arbitrary specificity onto an immune effector cell, usually a specific monoclonal antibody. When T cells express this molecule, they then recognize and kill target cells that express the matching antigen. This biological engineering of T cells represents an important emerging immunotherapy that can target and kill cancer cells displaying specific immune fingerprints. However, despite the immense potential, there are still challenges associated with toxicity, off-target effects, and uneconomical manufacturing.
While Intrexon, a company employing modular DNA control systems to develop new therapies, holds the technology platforms, molecular engineering, systems biology, and cell engineering capabilities necessary to overcome these challenges, the utilization of the RTS® platform will facilitate regulation of one or more bioeffectors in CAR-T cells, allowing physicians to tightly regulate the dosage regimen to the oral activator ligand (veledimex), since the RTS® platform provides a mechanism for titrating therapeutic effects on a patient-specific and predictable basis, as well as a safety switch to rapidly turn off gene-expression.
Samuel Broder, M.D., EVP of Scientific and Public Affairs at Intrexon, said, “As a leader in the second generation of biotechnology, Intrexon is applying industrial engineering principles to synthetic immunology to potentiate important biotechnology platforms enabling end-to-end solutions for complex biologic challenges. In particular, the utilization of our proprietary RheoSwitch® platform may be especially advantageous in CAR-T treatments.”
More than 1,000 Phase I or Phase II clinical trials utilizing gene therapy are currently ongoing. Intrexon’s proprietary switch system is the first clinically evaluated gene switch providing in vivo data demonstrating its ability to control gene expression with a broad dynamic range.
“We are excited by the prospects of applying our advanced synthetic immuno-oncology toolkit towards targeted immunotherapies like CAR-T,” said Jonathan Lewis, M.D., Ph.D., CEO of ZIOPHARM. “We also look forward to expanding RTS® applications in novel therapeutic strategies for cancer where the ability to control gene expression is essential,” he added.
Regarding the Ad-RTS-IL-12 clinical programs, ZIOPHARM has ongoing Phase II clinical trials in melanoma and breast cancer using Ad-RTS-IL-12 as a monotherapy, and is envisioning trials using IL-12 in combination therapies with other immune-targeting agents in various cancers including melanoma and breast. Moreover, ZIOPHARM plans to initiate a Phase I trial to evaluate Ad-RTS-IL-12 as a single agent in the treatment of patients with Glioblastoma Multiforme in the second half of 2014.
Ad-RTS-IL-12 is a novel DNA-based therapeutic candidate given through an intratumoral injection. An adenoviral vector is delivered, directly employing a gene expressing Interleukin-12, a potent anticancer cytokine whose production can be tightly regulated by the RTS® platform.
“The development of potent yet tightly controlled cancer depleting therapies such as CAR-T and other targeted cellular products through the molecular rewiring of immunologic gene programs adds to the foundation of our multifaceted strategy in synthetic immuno-oncology,” stated Gregory Frost, Ph.D., SVP of Intrexon’s Health Sector.
ZIOPHARM and Intrexon are expected to provide their results update later this year.